title: "Click" conjugation of peptide on the surface of polymeric nanoparticles for targeting tumor angiogenesis.
abstract: OBJECTIVE
  Angiogenesis plays a critical role in tumor growth. This phenomena is regulated by numerous mediators such as vascular endothelial growth factor (VEGF). CBO-P11, a cyclo-peptide, has proven to specifically bind to receptors of VEGF and may be used as targeting ligand for tumor angiogenesis. We herein report the design of novel nanoparticles conjugated to CBO-P11 in order to specifically target tumor site.
  
  
  METHODS
  The conjugation of CBO-P11 on the surface of poly(vinylidene fluoride) (PVDF) nanoparticles was investigated using the copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition known as "click" reaction. CBO-P11 was modified with a near-infrared cyanine dye bearing an alkyne function, allowing both "click" coupling on azido-modified nanoparticles and fluorescence labelling. Each step of this nanodevice construction was judiciously performed in aqueous solution and successfully characterized. The cytotoxicity of nanoparticles was evaluated in human brain endothelial cell line and their affinity for VEGF receptors was determined via fluorescence-based uptake assays on porcine aortic endothelial cell line.
  
  
  RESULTS
  Nanoparticles were found to be spherical, dense, monodisperse and stable. No cytotoxicity was observed after four days of incubation demonstrating the biocompatibility of nanoparticles. Fluorescence highlighted the specific interaction of these functionalized nanoparticles for VEGF receptors, suggesting that the targeting peptide bioactivity was retained.
  
  
  CONCLUSIONS
  These results demonstrate the potential of these functionalized nanoparticles for targeting tumor angiogenesis and their possible use as multifunctional platform for cancer treatment if coupled with therapeutic agents.
authors.affiliation: CNAB, Chimie Bio-Organique, UMR CNRS 5084, Université de Bordeaux 2, 33076, Bordeaux, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Deshayes
authors.forename: Victor
authors.initials: V
authors.lastname: Maurizot
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Clochard
authors.forename: Cécile
authors.initials: C
authors.lastname: Baudin
authors.forename: Thomas
authors.initials: T
authors.lastname: Berthelot
authors.forename: Stéphane
authors.initials: S
authors.lastname: Esnouf
authors.forename: Didier
authors.initials: D
authors.lastname: Lairez
authors.forename: Michel
authors.initials: M
authors.lastname: Moenner
authors.forename: Gérard
authors.initials: G
authors.lastname: Déléris
mesh_terms: D000818:Animals; D002460:Cell Line; D057930:Click Chemistry; D016503:Drug Delivery Systems; D016228:Endothelial Growth Factors / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010455:Peptides / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013552:Swine; D005465:Fluorocarbon Polymers
chemical_list: D016228:Endothelial Growth Factors; D010455:Peptides; D010456:Peptides, Cyclic; D011145:Polyvinyls; D040262:Receptors, Vascular Endothelial Growth Factor; C478485:cyclo-VEGI; C024865:polyvinylidene fluoride; D005465:Fluorocarbon Polymers